Spatial and Spatio-temporal Epidemiology 21 (2017) 5766

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Spatial and Spatio-temporal Epidemiology

journal homepage: www.elsevier.com/locate/sste

Original Research

Environmental risk factors for the incidence of cutaneous

leishmaniasis in an endemic area of Iran: A GIS-based
approach
Roghieh Ramezankhani a,c, Arezoo Hosseini b, Nooshin Sajjadi c,
Mostafa Khoshabi d, Azra Ramezankhani e,
a
Center of Disease Control and Prevention, Ministry of Health of Iran, Tehran, Iran
b
Department of Geodesy and Geomatics Engineering, Shahid Rajaee Teacher Training University, Tehran, Iran
c
Department of Environment, Islamic Azad University, North Tehran Branch, Tehran, Iran
d
Department of Geo-Spatial Information System (GIS), Center of Excellence in GIS, K.N. Toosi University of Technology, Tehran, Iran
e
Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical
Sciences, Tehran, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: This study was designed to determine the environmental factors associated
Received 27 August 2016 with cutaneous leishmaniasis (CL) in Isfahan Province, using spatial analysis.
Revised 19 October 2016
Methods: Data of monthly CL incidence from 2010 to 2013, climate and environmental
Accepted 16 March 2017
factors including: temperature, humidity, rainfall, wind speed, normalized difference veg-
Available online 23 March 2017
etation index (NDVI), altitude and population density across the Isfahans cities was used
Keywords: to perform spatial analysis by ordinary least square (OLS) regression and geographically
Geographic information system weighted regression (GWR).
Geographically weighted regression Results: OLS revealed a signicant correlation between CL incidence and ve predictors in-
Environmental factor cluding temperature, population density, wind speed, humidity and NDVI; which explained
Cutaneous leishmaniasis 28.6% of variation in CL incidence in the province. Considering AICc and adjusted R2 , GWR
provided a better t to the data compared with OLS.
Conclusion: There was a positive correlation between temperature and population density
with CL incidence in both local (city) and global (province) level.
2017 Elsevier Ltd. All rights reserved.

1. Introduction a protozoan parasite of the family Trypanosomatidae that

Leishmaniasis is one of the most important vector-
borne diseases of humans with public health importance
in 88 countries worldwide especially, tropical and subtrop-
ical ones with prevalence of 12 million people and an in-
cidence of two million new cases each year (Matos et al.,
2008; Alvar et al., 2012; Davami et al., 2013). This para-
sitic disease can be caused by many species of Leishmania,
Corresponding author.
E-mail address: ma.ramezankhani@gmail.com (A. Ramezankhani).
infects humans and other mammals (WHO, 2010). Approx-
imately 30 species of parasite have been described, most
of which are zoonotic (Bates, 2007). Leishmanias develop
in foregut of insect vectors (sandies) and are transmitted
via bite to the tissues of vertebrate hosts (animals and hu-
man). In humans, different species of the parasite are as-
sociated with different forms of the disease. There are 3
main forms of leishmaniasis: cutaneous leishmaniasis (CL)
(skin ulcers), mucocutaneous leishmaniasis, and visceral
leishmaniasis (lethal spleen/liver inammation) (Reithinger
et al., 2007; Banuls et al., 2011). CL is the most common
form of leishmaniasis and causes ulcers on the exposed

http://dx.doi.org/10.1016/j.sste.2017.03.003
1877-5845/ 2017 Elsevier Ltd. All rights reserved.
58 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766
parts of the body, leaving scars for life (Reithinger et al.,
2007; Banuls et al., 2011). About 95% of CL cases occur in
the Americas, the Mediterranean, the Middle East and Cen-
tral Asia. More than two thirds of new cases of CL occur
in six countries: Afghanistan, Algeria, Brazil, Colombia, Iran
and Syria (Alvar et al., 2012).
Recent studies have shown that the geographical
distribution and abundance of vectors and reservoirs of
Leishmaniasis is directly or indirectly can be inuenced
by environmental factors (weather parameters, vegetation
and topography changes) (Patz et al., 2008; WHO, 2010),
man-made changes (rapid and unplanned urbanization,
development of new projects e.g., road and dams building,
mining, agricultural projects, forestry development, mil-
itary activities) and deterioration in social and economic
conditions in the poor suburbs of cities (Kelly-Hope and
Thomson 2008; WHO, 2010; Ready, 2008).
Leishmaniasis control program was initiated in 1966 in
Iran (Khademvatan et al., 2017). The disease exists in more
than 17 provinces of Iran. Despite the preventive programs
and national and international investments for CL control,
the disease still exists in many provinces, with an aver-
age of more than 22,0 0 0 cases in the last decade (Oshaghi
et al., 2010). Isfahan province is one of the most impor-
tant endemic areas of CL in Iran, with approximately 3378
new cases in 2013. Leishmania major is a main cause of CL
in humans in Isfahan, with Rhombomys opimus, a domes-
tic rodent, as the reservoir host and Phlebotomus papatasi
as its sand y vector (Rajabi et al., 2016; Nilforoushzadeh
et al., 2014).
In recent years, global climate change has occurred in
our country (Amiri and Eslamian, 2010; Alvar et al., 2012)
which led to increased attention to the impact of climate
change on the incidence and prevalence of CL in differ-
ent provinces of Iran (Ali-Akbarpour et al., 2012; Mollalo
et al., 2014, 2015). In addition, Isfahan Province has ex-
perienced some dangerous environmental changes such as
rapid expansion of cities, migration from rural to urban ar-
eas, construction projects, and drying the river Zayandeh-
Rud (Gohari et al., 2013). Therefore studying the possi-
ble climate and environmental change impacts on the CL
incidence in this endemic area of Iran is essential. Re-
cent advances in remote sensing techniques and computer-
based geographical information systems (GIS) during the
last 30 years have provided more powerful and ecient
tools to map vector-borne diseases and analyze environ-
mental factors affecting their spatial and temporal distribu-
tion (Moore and Carpenter, 1999; Hipp and Chalise, 2015;
Mollalo et al., 2015). GIS are powerful automated systems
for the capture, storage, retrieval, analysis, and display of
spatial data (Clarke et al., 1996). Recently GIS has been
used in a broad range of studies including the surveillance
and monitoring of vector-borne diseases, water borne dis-
eases, and environmental health (Eisen and Eisen, 2011;
Hashemi Beni et al., 2012; Gale et al., 2011; Barnes et al.,
2015).
In spite of broad studies on the association between
environmental factors and CL incidence throughout the
world, very little researches in this regard have been re-
ported from Iran. Therefore, the present study aimed to ap-
ply the GIS for identication of spatial distribution of the
CL cases in the Isfahan Province and also, use of two GIS-
based modeling approaches for determining of the most
important climatic and environmental factors affecting the
CL incidence in this province.
2. Methods
2.1. Site description
The Isfahan province is located in the central part of
Iran. It has an area of 115,932 km2 lying within the 3143
3422 N and 4938 55 31 E. Isfahan consisting of the 23
cities and 4,629,312 inhabitants (according to 2011 esti-
mates). Due to varying altitudes in various regions, Isfa-
han has three types of weather: very arid to warm arid
weather, semi humid to cold humid weather and semi-
arid weather. Therefore, this province is considered as
arid and semiarid regions of the Iran. The province has a
moderate and dry climate on the whole, ranging between
40.6 and 10.6 C on a cold day in the winter season. The
average annual temperature has been recorded as 15.6 C
and the annual rainfall on an average has been reported as
125 mm (Shafaghi, 2007) (Fig. 1).
2.2. Data collection and preparation
Data included CL incident data, information on popula-
tion at risk for each city, environmental and climate data.
2.2.1. CL incident data
All cases of leishmaniasis in Iran are required to be re-
ported to the health care centers when they are diagnosed
by doctors or laboratories. Then, health care staffs must
report the conrmed cases to the center for disease con-
trol and prevention (CDC) department in the ministry of
health. The patients are referred to the city or province
health care centers for diagnosis of CL based on clinical
observation, positive smear and culture assay. Case deni-
tions are based on the national control guidelines for cuta-
neous and visceral leishmaniasis (Shirzadi et al., 2015). In
this study, the data on the number of CL cases in Isfahan
Province were collected from CDC department in the min-
istry of health from 2010 to 2013 (April 2010 to December
2013). During this period, a total of 13,337 cases of CL from
Isfahan Province were ocially reported.
2.2.2. Population at risk
The estimated population census counts in each city of
Isfahan Province were obtained from the statistical center
in Iran for the period 20102013. The monthly incidence
rate of CL in each city was dened as follows:
Monthly incidence rate = (total number of CL cases per
month / total population at risk) 10 0,0 0 0
2.2.3. Climate and environmental data
Climate data: These data included temperature, rela-
tive humidity, rainfall, and wind speed, which were col-
lected from 31 synoptic stations in Isfahan province and
six adjacent provinces (Markazi, Qom, Semnan, Fars, Ko-
hgiluyeh VA Boyer Ahmad) during the study period (April
2010December 2013). For preparation of climate data, we
 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766
Fig. 1. Geographic location of the Isfahan province and its cities, center of Iran.
rst computed the monthly average of the all climatic
parameters in each synoptic station; then, a raster sur-
face, with a pixels size of 100 m, was created from points
data (monthly average) using an inverse distance weighted
(IDW) technique. Finally, monthly average of four climatic
parameters was obtained from raster surface (pixels size of
100 m) using zonal statistics, separately for each city.
Herb coverage data: In order to assess vegetation cover
of the study area, we obtained normalized difference veg-
etation index (NDVI) using time series of moderate res-
olution imaging spectroradiometer (MODIS) (16-day com-
posites) with 250 m spatial resolution (Vuolo et al., 2012),
derived from MODIS website. As NDVI metric was con-
stant during 20102013 (US Geological Survey, 2014), we
obtained the NDVI for the year of 2011 (middle of dura-
tion) separately for each month (Fig. 2). Then, the monthly
average of NDVI was obtained separately for each city us-
ing zonal statistic.
Altitude: The elevation of each city was derived from
250 250 m spatial resolution digital elevation models
(DEM) of global topography. A DEM is a gridded array
of elevations that provided by remote sensing data. We
downloaded the DEM data through the USGS WEB site
(USGS Global Data Explorer 2014). Then zonal statistics
was applied for computing average of altitude for each city.
2.3. Geographically weighted regression
Due to use of spatial data in our study, we used geo-
graphic weighted regression (GWR) for the analysis of CL
incidence data. GWR is a spatial analysis technique that
59
takes non-stationary variables into consideration (e.g., cli-
mate; environmental factors) and models the local rela-
tionships between these predictors and an outcome of in-
terest. GWR is an outgrowth of ordinary least squares re-
gression (OLS); and adds a level of modeling sophistica-
tion by allowing the relationships between the indepen-
dent and dependent variables to vary by locality. It also
accounts for spatial autocorrelation of variables. Briey,
GWR constructs a separate OLS equation for every location
(city) in the dataset and produce a range of coecients
(Fotheringham and Brunsdon, 1999).
2.4. Methodological steps in model building
The rst step in the spatial analysis is to map the de-
pendent variable and explore spatial heterogeneity. If the
dependent variable is clustered, there is need to build
a spatially explicit model using GWR (Fotheringham and
Brunsdon, 1999). We used the Morans Index (Morans I)
for assessing the heterogeneity of CL cases across cities
in the Province. The Morans I score ranges from 1 (dis-
persed) to 1 (clustered); a value of 0, or very close to 0,
refers to random distributions (Moran, 1948). As the preva-
lence of CL cases in our data was highly clustered, we
moved to GWR for model building as follows:
(1) At rst we divided the data into two parts: data
from 2010 to 2012, which was used for model building,
and data of 2013 for testing the performances of the mod-
els. (2) The monthly average incident rate (percent) was
dened as the dependent variable; and, environmental, cli-
matic factors and population density were considered as
60 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766

Fig. 2. Monthly NDVI in Isfahan province of Iran in 2011.

independent variables. (3) Because dependent variable (CL
incidence) was a continuous variable, its distribution was
checked for normality. (4) As the distribution of the depen-
dent variable was close to normal, the OLS model was run
to determine the global regression coecients ( ) for the
independent variables. In the OLS model we assessed the
multi-collinearity between predictors using variance ina-
tion factor (VIF); the collinear variables was then excluded
from the model and nal OLS model was developed us-
ing the remaining predictors. The spatial independency of
residuals in the OLS model was evaluated by Morans I. To
assess stationarity in the OLS model, the Koenkers studen-
tized BrueschPagan statistic (Koenker (BP)) was obtained.
The JarqueBera statistic was used to assess the OLS model
bias. The JarqueBera statistic indicates whether or not the
residuals are normally distributed (Thadewald and Bn-
ing, 2007). (5) We developed the GWR model using the
same independent variables which were used for nal OLS
model. The residuals from the GWR model were analyzed
using Morans I to assess spatial autocorrelation. (6) The
 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766 61

Fig. 3. Annual CL incidence rate (Per 10 0,0 0 0) at the city level in Isfahan province, Iran, 20102013.

performances of the two models were compared using ad- Table 1

Preliminary results of the OLS model.
justed R2 , corrected Akaike information criteria (AICc) and
residuals of the models. (7) The predictive ability of the Parameters Coecients (??) P-value VIF
two OLS and GWR models were measured on the test Intercept 27.54 0.00

data. We used the root mean squared error (RMSE) for Population density 0.0 0 0 04 0.00 1.01
comparing the predictive ability of the two models. RMSE NDVI 0.005 0.00 1.19
measures the average of the squares of the errors that is Altitude 0.007 0.00 1.28
Humidity 0.11 0.19 4.61
the difference between the predicted value and observed
Temperature 0.04 0.79 2.32
value. Maximum wind speed 0.48 0.14 5.13
Arc GIS 10.2 was used for data preparation, obtaining Rainfall 0.04 0.48 2.27
Morans I and building OLS and GWR models. A p-value of R2 0.29
Adjusted R2 0.28
0.05 was considered as signicant.
AICc 7916.755

3. Results Coecients are related to the preliminary multivariable OLS

During the study period, a total of 13,337 CL cases
were reported. Fig. 3 shows the annual CL incidence rates
(cases per 10 0,0 0 0) at city level. Highest incident CL cases
were observed in Isfahan city. CL prevalence in the Isfa-
han Province was signicantly clustered (Morans I = 0.15;
z = 2.55; p = 0.01) (Fig. 3).
The train data (data from 2010 to 2012) and test data
(data from 2013) included 9959 and 3378 total incident
cases of CL, respectively. The following 7 variables were
included in the OLS model: population density, NDVI, al-
titude, humidity, temperature, maximum wind speed and
rainfall. Preliminary results of the OLS model are shown
in Table 1. CL incidence was signicantly correlated with
population density, NDVI and altitude (p < 0.001).
For obtaining optimum results, we removed variables
with large VIF one by one and testing the signicance of
adding or subtracting variables from the regression model
to prevent redundancy (collinearity). Finally, after omit-
ting rainfall and maximum wind speed, all the remaining
model including all seven independent variables.
Coecients are signicant at the 0.05 level.
VIF: Variance ination factor; NDVI: normalized difference vege-
tation index.
variables (population density, NDVI, altitude, humidity and
temperature) were signicantly correlated with the inde-
pendent variable (p < 0.05) (Table 2).
Adjusted R-squared for the OLS model showed that this
global regression model explained only 28.6 percent of the
total variance of CL incidence in Isfahan Province. Fig. 4
shows the standardized residuals plot of the nal OLS
model. The Morans I (Morans I = 0.045, Z = 5.91, p < 0.01)
showed that residuals were not spatially random. It means
that there were signicant spatial variations in the risk fac-
tors of CL incidence across Esfahan province.
The JarqueBera statistic (p < 0.05) showed that the
residuals were not normally distributed. Koenker statistic
(p < 0.05) indicated that data were not stationary; it means
that the ve predictor variables in the OLS model had not
62 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766

Fig. 4. Standardized residual plot of the nal OLS model in the study area.

Table 2 Province (Table 2). However, the GWR models show that
The results of the nal OLS model.
the coecients for this variable range from 0.104 to 0.067
Parameters Coecients (??) P-value VIF across the cities (Table 3). This variability in the model pa-
Intercept 28.25 0.00 rameter suggests that the relationship between humidity
Population density 0.0 0 0 03 0.00 1.01 and CL incidence is not stationary within the cities. Similar
NDVI 0.005 0.00 1.18 results can be observed in Table 3 for the other variables.
Altitude 0.008 0.00 1.18 Fig. 5 shows the standardized residuals plot of the GWR
Humidity 0.012 0.04 1.03
model. The Morans I (Morans = 0.021, Z = 2.81, p < 0.01)
Temperature 0.193 0.03 1.06
R2 0.290 showed that there was a signicant spatial autocorrelation
Adjusted R2 0.286 or signicant clustering in the residuals of the GWR model.
AICc 7915.44 Table 4 summaries the performance of two OLS and
Morans I 0.045 0.005
GWR model. Residuals for the GWR model, although sig-
JarqueBera statistic 3,6741.97 0.001
Koenker statistic 237.869 0.001 nicant, were less spatially auto-correlated than residuals
for the OLS model (Morans I = 0.021 vs. Morans I = 0.045).
AICc: Corrected Akaike information criteria.
The AIC is a recommended measure for comparing a global
VIF: Variance ination factor; NDVI: normalized difference veg-
etation index; Morans I: Morans Index. regression model with a GWR model (Fotheringham et al.,

Coecient is signicant at the 0.05 level 2003). The AICc score for the GWR (7897.01) was about
18.5 units smaller than the AICc from the global OLS model
(7915.44), which suggests that GWR provided a better t to
a consistent relationship to the dependent variable across the data compared with OLS (Table 3).
cities. Results of the testing two regression models on data
We used GWR to remove the effect of non-stationary from year 2013 (test data) showed that the overall er-
features of the data. In other words, a GWR model was ror rate was 7.2 and 6.8 (cases per 10 0,0 0 0 persons) per
applied to analyze how the relation between population month for OLS and GWR models, respectively. Fig. 6 shows
density, NDVI, altitude, humidity, temperature, maximum the RMSE for two models in each city in the year 2013;
wind speed and CL incidence changed from one city to an- as gure shows, the city of Isfahan has the highest RMSE
other. The GWR model produced regression coecients for among 23 cities.
each city. The summary results of the GWR are provided The nal OLS model is suggested in Eq. (1). The value
in Table 3. The GWR could explain 30.5 percent of the to- of coecients (???? to ??5) is shown in Table 2.
tal model variation with the AICc of 7897.01.
The GWR results allow us to examine the spatial varia-
tion within the study area for each individual variable. For CL incidence = ???? + ??1 (population density) ??2
example, OLS model estimated the parameter for the hu- (NDVI) ??3 (altitude) ??4 (humidity) + ??5
midity to be signicant and equal to 0.012 for the entire (temperature) (1)
 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766 63

Table 3
The results of the GWR model.

Parameters (??) Minimum (??) Maximum Standard error

Intercept 10.41 45.98 14.12

Population density 0.0 0 0 03 0.0 0 0 04 0.0 0 0 0 03
NDVI 0.016 0.002 0.003
Altitude 0.015 0.031 0.009
Humidity 0.104 0.067 0.048
Temperature 0.023 0.399 0.105
R2 0.320
Adjusted R2 0.305
AICc 7897.01

AICc: Corrected Akaike information criteria.

NDVI: Normalized difference vegetation index.

Fig. 5. Standardized residual plot of the GWR model in the study area.

Table 4 4. Discussion
Performances of the two OLS and GWR models.
The present study investigated the spatial distribution
Morans I R-squared Adjuste R-squared AICc

OLS 0.045 0.290 0.286 7915.44 of the CL cases and the impact of environmental factors
GWR 0.021 0.320 0.305 7897.01 on the incidence of CL in an endemic area of Iran. For

the analysis, we used two common methods of OLS and
AICc: Corrected Akaike information criteria
GWR, respectively. Results of the OLS residuals showed
that the relationships between CL incidence and predictors
were spatially nonstationary across the Isfahan province.
GWR generates a separate regression equation for each The same set of variables was then used to develop a GWR
city in the study area. Each GWR equation may be ex- model. Regarding AICc, GWR provided a better t to the
pressed as: data compared with OLS. However, there were no consid-
erable difference between global (OLS) and local (GWR)
CL incidence (ui ) = ???? + ??1 (ui ) (population models considering R2 and RMSE. There are numerous
density) + ??2 (ui ) (NDVI) + ??3 (ui ) (altitude) + ??4 studies in different area have shown better performance of
(ui ) (humidity) + ??5 (ui ) (temperature) (2) the GWR compared to OLS regarding R2 in spatial anal-
ysis of some diseases (Grillet et al., 2010; Haque et al.,
2012; Hipp and Chalise, 2015). This discrepancy can be due
In Eq. (2), (ui ) is the location of each city and (???? to to the limitation of GWR model in our study. GWR pro-
??5 ) are the model parameters for each city. vides the local regression equations in each city that are
64 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766
Fig. 6. Root mean squared errors (RMSE) of the two OLS and GWR models by the cities for the year 2013.
inuenced by bordering cities and other nearby cities;
however, the distance of inuence of predictors is theo-
retically unknown and may be inconsistent across a geo-
graphic area. If we could divide the cities into smaller sub-
sections, we might get different results. Secondly, the lo-
cal GWR model explained about one-third of the variance
in CL incidence (R2 = 30.5%), which means that most fac-
tors associated with city-level CL incidence must have been
missing from our models. Third, OLS and GWR are both
linear methods; the models will perform poorly, if rela-
tionship between any of the predictor variables and the CL
incidence is nonlinear. For example one study performed
in Pre-Saharan North Africa has shown that increased
minimum temperature following climate change, has cre-
ated conditions suitable for endemicity; but, temperatures
above a critical range suppress CL incidence by limiting the
vectors reproductive activity (Bounoua et al., 2013). There-
fore, the non-linear relationship between study variables
and CL incidence may not be revealed using GWR or OLS
methods.
The global OLS model in the present study explained
28.6% of CL incidence by the ve predictors included pop-
ulation density, NDVI, altitude, humidity and temperature.
The risk of CL incidence in some provinces of Iran has
previously been found to be associated with environmen-
tal factors such as vegetation cover (Mollalo et al., 2014)
and rain fall, temperature, wind speed and humidity (Ali-
Akbarpour et al., 2012).
Our results showed that in the nal OLS model the
regression coecients ( ) for temperature and humidity
yielded the highest value. Temperature had positive and
humidity had negative correlation with CL incidence. In a
similar study performed in Fars province of Iran, rain fall,
temperature, wind speed and humidity were the most im-
portant predictors of spatial distribution of CL incidence
(Ali-Akbarpour et al., 2012).
It is well understood that Leishmaniasis is strongly af-
fected by temperature and humidity directly, by the effect
of temperature on survival of sand y, development and
its activity (WHO, 2010; Hlavacova et al., 2013), or indi-
rectly by the effect of environmental variation on the range
and seasonal abundances of the vector species (Lawyer and
Perkins, 20 0 0). The worldwide distribution of sand y is
limited to areas that have at least one month with a mean
temperature of 20 C (Lawyer and Perkins, 20 0 0). Below
10 C, sand ies must enter a dormant state in order to
survive winter, therefore reducing the breeding population
(Medlock et al., 2014). Sand ies are sensitive to sudden
temperature changes and usually prefer those areas with a
small difference in maximum and minimum temperatures.
As climatic temperatures increases, it accelerates matura-
tion of the leishmania parasite, and also increasing the
risk of infection. However, if the climate conditions are too
hot and dry, vector survival rate is decreases and the dis-
ease may disappear from some area (Lawyer and Perkins,
20 0 0; Medlock et al., 2014). In addition to an appropri-
ate temperature, sucient moisture in the environment
is required for growth of sand ies, because humidity is
an important factor for egg survival (Lawyer and Perkins,
20 0 0). However, peaks in rainfall can lead to reductions in
sand y numbers because excess precipitation reduces the
amount of suitable resting sites for adult insects and limits
adult ight activity, as well as killing the eggs (Lawyer and
Perkins, 20 0 0; Medlock et al., 2014). Current studies in dif-
ferent part of the world show that at the places where the
temperature has risen, due to climatic changes, the preva-
lence of the CL increased many fold (Bounoua et al., 2013).
 R. Ramezankhani et al. / Spatial and Spatio-temporal Epidemiology 21 (2017) 5766
Results of the local GWR models in our study showed
that although the coecients for the temperature had a
range from 0.023 to 0.399 across cities in the province,
the direction of association was equal in all cities, which
is consistent with the global OLS regression model result.
Therefore, our analysis showed that air temperatures
have been positively associated with CL incidence in both
local (city) and global (province) level. Also, both GWR and
OLS revealed a signicantly positive association between
population density and CL incidence in local and global
level, respectively. In a similar study was conducted in
south of Iran, a signicant positive association was found
between population density and CL incidence in both local
and global level (Ali-Akbarpour et al., 2012).
We found a signicant negative association between
NDVI and altitude with CL incidence. One study conducted
in Golestan province (north of Iran) showed a negative sig-
nicant associations between the NDVI variables and CL
incidence; lack or low vegetation cover was a major de-
terminant of CL prevalence in that province (Mollalo et al.,
2014).
Although the global OLS model in our study produced
a negatively signicant coecient for the NDVI in entire
study area, GWR produced both negative and positive co-
ecients across cities. These variations in direction (coe-
cient signs) point to the need to assess statistical relation-
ships for environmental factors locally instead of globally.
In general, sand ies are found in dry areas, then, when
climate change tends to dryer weather conditions, vec-
tor populations could increase, and therefore, leishmaniasis
transmission may be higher (Cardenas et al., 2006). There
was substantial climatic variability during the study pe-
riod (20102013) in Isfahan; i.e., Zayanderood, the largest
river in Iran, completely dried out in the early 2010s, af-
ter several years of seasonal dry-outs (Gohari et al., 2013).
It is expected that this environmental change increase the
gerbil population which are the reservoirs of Leishmaniasis
disease and live under the ground in soil (Amoli, 2011).
Testing the nal OLS and GWR models on data from
2013 showed that the RMSE was higher in four large cities
of province. This indicates that in these large geographic
areas other factors must have been related to CL incidence.
Limitations of this study
This study is subject to several limitations. First, we did
not included some important factors such as demographic
data, human behaviors, seasonal, cycle and genetic varia-
tion of the vectors that are related to CL incidence; there-
fore, future researches are required to evaluate the effect
of other ecological and sociological factors which might
inuence the spatial and spatio-temporal patterns of the
disease in addition to climatic and environmental changes.
Second, incidence of CL cases may be underestimated due
to not reported to the health authorities, not diagnosed or
misdiagnosed cases. Third, short period of this study (three
years) may not be long enough to effectively meet the
changes in infectious disease patterns caused by climate
change. Finally, our data are not a nationally representa-
tive sample of the Iran, and so the external validity of OLS
65
or GWR models may be reduced due to a large variation in
the geographical size and shape of the units of analysis.
In the future, we will use data mining techniques such
as decision tree and neural network algorithms for explor-
ing nonlinear relationship between environmental factors
and CL incidence.
5. Conclusion
In conclusion, spatial analysis showed that climatic and
environmental factors in our study had not a consistent re-
lationship to the CL incidence in different geographic space
of Isfahan Province. This study demonstrates the utility of
GWR as a tool for ecological health research in our country.
Using the GWR or OLS we can explain 30% of the vari-
ance in the city level CL incidence. Based on Global OLS
model, temperature and humidity were the most impor-
tant climatic factors which had positive and negative as-
sociation, respectively, with CL incidence. However, GWR
showed that the impact of these factors also differed from
city to city across province.
The results of our study elucidate that conventional
multivariate regression (OLS) cannot reveal local variations
in the statistical relationships between CL risk and relevant
explanatory variables such as NDVI, humidity, and altitude
of the area. Local spatial statistical techniques such as GWR
are thus necessary to investigate spatial variations in rela-
tionships that are relevant to environmental factors.
Funding sources
This research did not receive any specic grant from
funding agencies in the public, commercial, or not-for-
prot sectors.
Conict of interest
The authors declare that they have no conict of inter-
est.
Acknowledgments
The authors wish to acknowledge the communicable
disease control department in ministry of health and med-
ical education who provided CL cases data. We especially
would like to acknowledge the health care staffs in the
health system network for assistance in data collection. We
also acknowledge the weather station of the provinces for
providing climate data.
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